We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Increased Expression of RhoA in Epithelium and Smooth Muscle of Obese Mouse Models: Implications for Isoprenoid Control of Airway Smooth Muscle and Fibroblasts.
- Authors
Ross, Kristie R.; Darrah, Rebecca J.; Hodges, Craig A.; Lang, LaTresa; Kelley, Thomas J.
- Abstract
The simultaneous rise in the prevalence of asthma and obesity has prompted epidemiologic studies that establish obesity as a risk factor for asthma. The alterations in cell signaling that explain this link are not well understood and warrant investigation so that therapies that target this asthma phenotype can be developed. We identified a significant increase in expression of the small GTPase RhoA in nasal epithelial cells and tracheal smooth muscle cells from leptin-deficient (ob/ob) mice compared to their wild-type counterparts. Since RhoA function is dependent on isoprenoid modification, we sought to determine the role of isoprenoid-mediated signaling in regulating the viability and proliferation of human airway smooth muscle cells (ASM) and normal human lung fibroblasts (NHLF). Inhibiting isoprenoid signaling with mevastatin significantly decreased the viability of ASM and NHLF. This inhibition was reversed by geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP), suggesting specificity to the Rho GTPases. Conversely, increasing isoprenoid synthesis significantly increased ASM proliferation and RhoA protein expression. RhoA expression is inherently increased in airway tissue from ob/ob mice, and obesity-entrained alterations in this pathway may make it a novel therapeutic target for treating airway disease in the obese population.
- Subjects
GENE expression; EPITHELIUM; SMOOTH muscle physiology; OBESITY in animals; LABORATORY mice; ISOPENTENOIDS; FIBROBLASTS; PREVENTIVE medicine; PHYSIOLOGY
- Publication
Journal of Allergy, 2013, p1
- ISSN
1687-9783
- Publication type
Article
- DOI
10.1155/2013/740973